Abstract: Herein are provided anti-CD22 single domain antibodies (sdAb) prepared by immunizing a llama with the extracellular domain of the predominant human CD22 isoform. By constructing a library of the heavy chain repertoire generated, VHH antibodies specific to the immunogen were isolated. The 27 example antibodies initially produced comprise CDR1, CDR2, and CDR3 sequences corresponding, respectively to SEQNOs: 1-3, 4-6, 7-9, 10-12, 13-15, 16- 18, 19-21, 22-24, 25-27, 28-30, 31-33, 34-36, 37-39, 40-42, 43-45, 46-48, 49-51, 52-54, 55- 57, 58-60, 61-63, 64-66, 67-69, 70-72, 73-75, 75-78, and 79-81; and related sequences. Also provided are multivalent antibodies comprising any one of the sdAbs, including bispecific T-cell engagers, bispecific killer cell engagers (BiKEs), and trispecific killer cell engagers (TriKEs). Also described are chimeric antigen receptors (CARs) for CAR-T therapy comprising any one of the aforementioned sdAbs. Uses of these molecules in the treatment of cancer are also described.

Abstract: The present disclosure relates to antigen-binding agents that specifically bind to epidermal growth factor receptor variant III (EGFRvIII). Antigen-binding agents of the present disclosure include antibodies and antigen-binding fragments thereof, chimeric antigen receptors (CARs) and bi-specific T-cell engagers (BITE!), bispecific killer cell engagers (BiKEs) and bispecific killer cell engagers (TriKEs). Nucleic acid molecules and vectors expressing antibodies, antigen-binding fragments, CARs, BiTEs, BiKEs or TriKEs are also encompassed by the present disclosure. Immune cells engineered to express CARs, BiTEs, BiKEs or TriKEs may be used to specifically recognize and kill cells expressing EGFRvIII.

Abstract: Antigen-binding agents such as antibodies or antigen-binding fragments thereof, chimeric antigen receptors (CARs), bispecific T-cell engagers (BiTEs) and the like that specifically bind to epidermal growth factor receptor variant III (EGFRvIII) are provided. The EGFRvIII-specific antibodies or antigen-binding fragments, CARs and BiTEs thereof may be used for the treatment of cancer. Antibody drug conjugates targeting EGFRvIII-expressing cells are particularly contemplated.